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Article: Incidence of RET mutations in patients with Hirschsprung's disease

TitleIncidence of RET mutations in patients with Hirschsprung's disease
Authors
Issue Date2000
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurg
Citation
Journal of Pediatric Surgery, 2000, v. 35, p. 139-143 How to Cite?
AbstractBackground: Ret Mutations Have Been Reported Variously To Affect 7% To 41% Of Hirschsprung's Disease (Hscr) Patients Depending On Familial Or Sporadic Occurrence Of The Disease, Length Of Aganglionosis And Possible Association With Other Disease Phenotypes. The Authors Report A Study Of The Incidence Of Ret Mutations In Unselected Hscr Patients From Two Regional Centers And Correlate Their Genotypes And Phenotypes. Methods: The Records Of Hscr Patients Treated In 2 Regional Centers With A Combined Population Of 5 Million Were Reviewed, And Blood Samples Were Obtained From 57 Patients. During The Same Period, 39 Patients With Similar Demographic Data Refused Or Provided Insufficient Blood For Study. Dna Was Extracted And The 21 Exons Of The Ret Proto-Oncogene Were Screened For Mutations Using Denaturing Gradient Gel Electrophoresis (Dgge). Results: Of 57 Patients, 48 Were Sporadic, And 9 Were Familial. Lengths Of Aganglionosis Were Total Colonic, 4; Long, 11; Short, 39; Ultrashort, 1; Unclassified, 2. Associated Anomalies Were Present In 20. Causative Mutations Were Identified In 4 (7%): Missense Or 'Silent' In 3 (Exons 5, 11, 13) And Deletion In 1. The Silent Mutation Of Exon 11 Recently Has Been Shown To Have Effects On Correct Ret Mrna Splicing. One Mutation Occurred In Total Colonic Aganglionosis (25%), 1 In Long Segment Dysganglionosis (9%), And 2 In Short Segment Aganglionosis (5%). Surprisingly, All These Mutations Occurred In Sporadic Cases (10%). Five Patients (9%) Had Rare Polymorphic Alleles At Exons 14 (N = 1) And Exon 18 (N = 4). Fifty Patients (88%) Showed Common Polymorphic Alleles (Sequence Variants) In 1 Or More Exons (>4, N = 5). Conclusions: Ret Mutation As A Primary Cause For Hirschsprung's Disease In The General Surgical Population Is Less Frequent Than Previously Thought. This Observation Is Compatible With The Hypothesis That Hscr Could Be A Polygenic Disease Caused By Additive Subclinical Effects Of More Than One Gene, Including Ret.
Persistent Identifierhttp://hdl.handle.net/10722/84206
ISSN
2015 Impact Factor: 1.733
2015 SCImago Journal Rankings: 0.802
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSancandi, Ten_HK
dc.contributor.authorCeccherini, Ien_HK
dc.contributor.authorCosta, Men_HK
dc.contributor.authorFava, Men_HK
dc.contributor.authorChen, Ben_HK
dc.contributor.authorWu, Yen_HK
dc.contributor.authorHofstra, Ren_HK
dc.contributor.authorLaurie, Ten_HK
dc.contributor.authorGriffths, Men_HK
dc.contributor.authorBurge, Den_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T08:50:13Z-
dc.date.available2010-09-06T08:50:13Z-
dc.date.issued2000en_HK
dc.identifier.citationJournal of Pediatric Surgery, 2000, v. 35, p. 139-143en_HK
dc.identifier.issn0022-3468en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84206-
dc.description.abstractBackground: Ret Mutations Have Been Reported Variously To Affect 7% To 41% Of Hirschsprung's Disease (Hscr) Patients Depending On Familial Or Sporadic Occurrence Of The Disease, Length Of Aganglionosis And Possible Association With Other Disease Phenotypes. The Authors Report A Study Of The Incidence Of Ret Mutations In Unselected Hscr Patients From Two Regional Centers And Correlate Their Genotypes And Phenotypes. Methods: The Records Of Hscr Patients Treated In 2 Regional Centers With A Combined Population Of 5 Million Were Reviewed, And Blood Samples Were Obtained From 57 Patients. During The Same Period, 39 Patients With Similar Demographic Data Refused Or Provided Insufficient Blood For Study. Dna Was Extracted And The 21 Exons Of The Ret Proto-Oncogene Were Screened For Mutations Using Denaturing Gradient Gel Electrophoresis (Dgge). Results: Of 57 Patients, 48 Were Sporadic, And 9 Were Familial. Lengths Of Aganglionosis Were Total Colonic, 4; Long, 11; Short, 39; Ultrashort, 1; Unclassified, 2. Associated Anomalies Were Present In 20. Causative Mutations Were Identified In 4 (7%): Missense Or 'Silent' In 3 (Exons 5, 11, 13) And Deletion In 1. The Silent Mutation Of Exon 11 Recently Has Been Shown To Have Effects On Correct Ret Mrna Splicing. One Mutation Occurred In Total Colonic Aganglionosis (25%), 1 In Long Segment Dysganglionosis (9%), And 2 In Short Segment Aganglionosis (5%). Surprisingly, All These Mutations Occurred In Sporadic Cases (10%). Five Patients (9%) Had Rare Polymorphic Alleles At Exons 14 (N = 1) And Exon 18 (N = 4). Fifty Patients (88%) Showed Common Polymorphic Alleles (Sequence Variants) In 1 Or More Exons (>4, N = 5). Conclusions: Ret Mutation As A Primary Cause For Hirschsprung's Disease In The General Surgical Population Is Less Frequent Than Previously Thought. This Observation Is Compatible With The Hypothesis That Hscr Could Be A Polygenic Disease Caused By Additive Subclinical Effects Of More Than One Gene, Including Ret.en_US
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurgen_HK
dc.relation.ispartofJournal of Pediatric Surgeryen_HK
dc.titleIncidence of RET mutations in patients with Hirschsprung's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3468&volume=35&spage=139&epage=143&date=2000&atitle=Incidence+of+RET+mutations+in+patients+with+Hirschsprung%27s+diseaseen_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10646792-
dc.identifier.scopuseid_2-s2.0-0033973161en_US
dc.identifier.hkuros48088en_HK
dc.identifier.volume35en_US
dc.identifier.issue1en_US
dc.identifier.spage139en_US
dc.identifier.epage143en_US
dc.identifier.isiWOS:000085007100051-

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